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S1065 Endoscopic and Histologic Remission After 2 Years Treatment With Mirikizumab in Patients With Moderately-to-Severely Active Ulcerative Colitis

2023· article· en· W4387750836 on OpenAlex
Fernando Margo, Laurent Peyrin‐Biroulet, Taku Kobayashi, Vipul Jairath, Alissa Walsh, Britt Christensen, Jianmin Wu, G Park, Isabel Redondo, Bruce E. Sands

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueThe American Journal of Gastroenterology · 2023
Typearticle
Languageen
FieldMedicine
TopicMicroscopic Colitis
Canadian institutionsWestern University
Fundersnot available
KeywordsMedicineUlcerative colitisInternal medicineGastroenterologySurgeryEndoscopyPhases of clinical researchClinical trialDisease

Abstract

fetched live from OpenAlex

Introduction: Mirikizumab (miri), a p19-directed IL-23 antibody, has shown efficacy in achieving clinical, endoscopic and histological response and remission after 52 weeks of therapy in patients with moderately-to-severely active ulcerative colitis (UC) in Phase 3 trials (LUCENT-1,; LUCENT-2). Histological healing in UC can indicate remission depth. Here, we report from LUCENT-3 the proportion of patients with and without prior biologic or tofacitinib failure who achieved histologic and endoscopic remission after 2 years of miri treatment. Methods: LUCENT-3 is an ongoing, single-arm, outpatient, multicenter, long-term extension Phase 3 study evaluating the efficacy and safety of miri in patients with moderately-to-severely active UC. All enrolled patients received open-label subcutaneous miri 200 mg every 4 weeks. This analysis focused on miri responders at Week (W)52 (patients who were responders at W12, were re-randomized to miri maintenance and were in response at the end of LUCENT-2) who were enrolled in the long-term extension and continued to receive miri for additional 52 weeks. Endpoints of interest are the proportions of patients with histologic improvement, endoscopic remission, endoscopic normalization, histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR), and alternate HEMR (histologic remission and endoscopic normalization) at W104. P-values were calculated using Pearson chi-square test. Missing response data were imputed as non-response. Results: Among the Week 52 miri responders (N=239), 60.3% were male, with mean age of 43.9. Mean baseline modified Mayo Score was 6.7, and 33.5% had prior biologic or tofacitinib exposure. After 2 years of miri treatment, 65.3% patients achieved endoscopic remission and 51.9% achieved histologic remission. HEMI and HEMR were achieved by 53.1% and 47.7% of patients, respectively. A similar proportion of patients achieved histologic improvement, histologic remission, endoscopic remission, HEMI, and HEMR irrespective of prior biologic or tofacitinib failure, with only endoscopic normalization and alternate HEMR showing statistically significant higher rates for patients who didn´t have prior biologic or tofacitinib failure (Table 1). Conclusion: In LUCENT-3, sustained histologic and endoscopic remission were observed in patients with moderately-to-severely active UC who were treated with mirikizumab for 2 years, regardless of previous biologic or tofacitinib failure. Table 1. - Proportion of Patients with Histologic and Endoscopic Outcome at Week 104 by Prior Biologic or Tofacitinib Treatment Failure Status at Baseline Mirikizumab Response Rates at Week 104 Prior Biologic or Tofacitinib Not Failed (N=166) Prior Biologic or Tofacitinib Failed (N=73) Overall (N=239) Histologic improvement a 99 (59.6%) 43 (58.9%) 142 (59.4%) Histologic remission b 85 (51.2%) 39 (53.4%) 124 (51.9%) Endoscopic remission c 114 (68.7%) 42 (57.5%) 156 (65.3%) HEMI d 90 (54.2%) 37 (50.7%) 127 (53.1%) HEMR e 80 (48.2%) 34 (46.6%) 114 (47.7%) Endoscopic normalization f 56 (33.7%) 13 (17.8%) * 69 (28.9%) Alternate HEMR g 48 (28.9%) 11 (15.1%) * 59 (24.7%) Data presented as n (%); P-value, *P< 0.05. Abbreviations: ES = Endoscopic Subscore; HEMI = Histologic Endoscopic Mucosal Improvement; HEMR = Histologic Endoscopic Mucosal Remission.aGeboes score≤3.1.bGeboes score≤2B.0.cES=0 or 1, excluding friability.dGeboes score≤3.1 and ES=0 or 1, excluding friability.eGeboes score≤2B.0 and ES=0 or 1, excluding friability.fES=0.gES=0 and Geboes score≤2B.0.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.414
Threshold uncertainty score0.370

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.243
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it